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Transition State Complex (transition + state_complex)
Selected Abstracts2-[(Imidazolylthio)methyl]pyrrolidine as a Trifunctional Organocatalyst for the Highly Asymmetric Michael Addition of Ketones to NitroolefinsEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 6 2008Dan-Qian Xu Abstract The direct asymmetric Michael addition of ketones to nitroolefins catalyzed by 2-[(imidazol-2-ylthio)methyl]pyrrolidine, constructed from natural L -proline and imidazolylthio platforms, with salicylic acid as a co-catalyst has been developed to give the products in high yields (up to 95,%) and with excellent enantioselectivities (up to 99,% ee). The highly efficient catalytic performance may be attributed to the dual activation of the Michael substrates by the trifunctional organocatalysts and the co-catalyst salicylic acid, leading to the formation of a stable transition state complex through the synergic effect of hydrogen-bonding and electrostatic interactions. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008) [source] Inhibition of acetylcholinesterase by physostigmine analogs: Conformational mobility of cysteine loop due to the steric effect of the alkyl chainJOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY, Issue 2 2002Enrico Gavuzzo Abstract The effect of a series of physostigmine analogs on acetylcholinesterase activity was investigated. The second-order rate constant kon of the enzyme,inhibitor complex correlates with the conformational positioning of aromatic residues, especially Trp84, in the transition state complex. The van der Waals interactions are an important structural element of this conformational change. A transient mobility of the cysteine loop (Cys67,Cys94) was confined only to the presence of a significant steric effect. Even with this limitation, however, the steric effect seems to be an appropriate model for future tests on the "back door" hypothesis involving facilitated opening for faster product clearance. © 2002 Wiley Periodicals, Inc. J Biochem Mol Toxicol 16:64,69, 2002; Published online in Wiley Interscience (www.interscience.wiley.com). DOI 10.1002/jbt.10026 [source] A novel method for enzyme designJOURNAL OF COMPUTATIONAL CHEMISTRY, Issue 2 2009Xiaolei Zhu Abstract Rational design of enzymes is a stringent test of our understanding of protein structure and function relationship, which also has numerous potential applications. We present a novel method for enzyme design that can find good candidate protein scaffolds in a protein-ligand database based on vector matching of key residues. Residues in the vicinity of the active site were also compared according to a similarity score between the scaffold protein and the target enzyme. Suitable scaffold proteins were selected, and the side chains of residues around the active sites were rebuilt using a previously developed side-chain packing program. Triose phosphate isomerase (TIM) was used as a validation test for enzyme design. Selected scaffold proteins were found to accommodate the enzyme active sites and successfully form a good transition state complex. This method overcomes the limitations of the current enzyme design methods that use limited number of protein scaffold and based on the position of ligands. As there are a large number of protein scaffolds available in the Protein Data Band, this method should be widely applicable for various types of enzyme design. © 2008 Wiley Periodicals, Inc. J Comput Chem, 2009 [source] Analysis of the plasticity of location of the Arg244 positive charge within the active site of the TEM-1 ,-lactamasePROTEIN SCIENCE, Issue 10 2009David C. Marciano Abstract A large number of ,-lactamases have emerged that are capable of conferring bacterial resistance to ,-lactam antibiotics. Comparison of the structural and functional features of this family has refined understanding of the catalytic properties of these enzymes. An arginine residue present at position 244 in TEM-1 ,-lactamase interacts with the carboxyl group common to penicillin and cephalosporin antibiotics and thereby stabilizes both the substrate and transition state complexes. A comparison of class A ,-lactamase sequences reveals that arginine at position 244 is not conserved, although a positive charge at this structural location is conserved and is provided by an arginine at positions 220 or 276 for those enzymes lacking arginine at position 244. The plasticity of the location of positive charge in the ,-lactamase active site was experimentally investigated by relocating the arginine at position 244 in TEM-1 ,-lactamase to positions 220, 272, and 276 by site-directed mutagenesis. Kinetic analysis of the engineered ,-lactamases revealed that removal of arginine 244 by alanine mutation reduced catalytic efficiency against all substrates tested and restoration of an arginine at positions 272 or 276 partially suppresses the catalytic defect of the Arg244Ala substitution. These results suggest an evolutionary mechanism for the observed divergence of the position of positive charge in the active site of class A ,-lactamases. [source] | ||||||||||